The primary targets for any dosage formulation is to deliver the necessary concentration of an active drug to the site of action to elicit the desired therapeutic response and to maintain an effective concentration of the drug for a sufficient period to achieve efficacious treatment. Oral administration is generally preferred but is frequently dependent upon the bioavailability of the active form of the drug, i.e., the rate and extent that the active form of the drug appears from the dosage form in the systemic circulation. Bioavailability is affected by the drug's physical chemical properties, such as pKa, water solubility, oil solubility and stability, as well as its absorption, distribution, metabolism and excretion. It is well known that water insoluble drugs are not generally available for absorption through intestinal lumin and oil insoluble drugs are generally unable to pass across intestine cell membranes into systemic circulation (S. H. Yalkowsky, “DRUGS AND THE PHARMACEUTICAL SCIENCES: TECHNIQUES OF SOLUBILIZATION OF DRUGS,” Marcel Dekker, Inc., Vol. 12, 1981). Proper formulation can improve the bioavailability of a drug.
Oral dosage formulations for water soluble or oil soluble drugs are well known. Oral dosage formulations for oil soluble drugs typically require that the oil form an aqueous emulsion. The emulsion may form in the stomach, for example an oil solution in soft gelatin capsules, or be prepared prior to consumption, for example mixing emulsifiable concentrates with an aqueous solution. In both cases, the oil should readily emulsify when released in an aqueous environment. Oils which rapidly emulsify without the use of sophisticated emulsification equipment, such as with gentle shaking or mixing, are known as self-emulsifiable oils. Dosage formulations that utilize such self-emulsifiable oils are known as self-emulsifying drug delivery systems or SEDDS (Charman et al., Pharm. Res. 9:87–93, 1992). Such self-emulsifiable oils are well known and include hydrocarbon oils combined with a surfactant (Iranloye and Pilpel, J. Pharm. Sci. 73:1267–1270, 1984) and vegetable oils combined with a non-ionic surfactant (Wakerly et al., J. Pharm. Pharmacol. 39:suppl. 6p, 1987). More recently, the use of polyglycolyzed glycerides with varying fatty acids and polyethylene glycols chain lengths were used in SEDDS formulations of hydrophobic drugs with adequate oil solubility (Shah et al., Int. J. Pharm. 106:15–23, 1994).
A problem arises when the drug is substantially insoluble in both water and oil. In such cases, the drug is typically poorly bioavailable at best and traditional oral dosage formulations tend not to substantially improve its bioavailability.